Jose Americo Bubo Na Tchuto was involved in last week's unrest
The US has accused two senior military men from Guinea-Bissau of drug running.
Air force head Ibraima Papa Camara and former navy chief Jose Americo Bubo Na Tchuto have been named "drug kingpins".
Under the Drug Kingpin Act, financial sanctions have been imposed on the two men and US citizens are barred from doing business with them.
Guinea-Bissau is a major transit point for cocaine smuggled from Latin America to Europe, and last week suffered an apparent army coup attempt.
Adam Szubin, head of the US Treasury's Office of Foreign Assets Control, said Mr Camara and Mr Na Tchuto have played "significant roles in international narcotics trafficking.
"Naming these two individuals as kingpins enables us to then target their facilitators, people who might be laundering money for them or assisting them in moving drugs," Mr Szubin told the BBC's Focus on Africa programme.
The two men will also have their US-based assets frozen.
One of the drug kingpins, Mr Na Tchuto, has been accused of plotting a 2008 coup and was due to be handed over to the government of Prime Minister Carlos Gomes Junior for trial.
But last week he emerged from a UN building in Bissau - where he had been taking refuge since December 2009 - and joined an apparent coup attempt led by army Vice Chief of Staff Gen Antonio Indjai.
During the unrest, soldiers entered the office of Mr Gomes and detained him along with the army Chief of Staff Gen Jose Zamora Induta.
The US fears the drugs trade will further destabilise the already volatile country.
"We certainly have noted with concern that the narcotics trafficking and the revenues from it play a destabilising role, not only in Guinea-Bissau, but in other countries in West Africa and throughout the world," said Mr Szubin.